STKE: Two Wnt Pathways

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Science  08 Oct 2004:
Vol. 306, Issue 5694, pp. 201c
DOI: 10.1126/science.306.5694.201c

Frizzled proteins act as receptors for Wnts, secreted proteins that play a critical role in animal development. In Caenorhabditis elegans vulval development, the anterior-posterior orientation of cells of the P7.p lineage is disrupted by mutation of lin-17 (which encodes a Frizzled protein) leading to a defect in morphology, the bivulva phenotype. Inoue et al. discovered that lin-18, mutations of which produce a similar bivulva phenotype, encodes the C. elegans member of the Ryk (related to tyrosine kinase)/Derailed protein family, which is not related to the Frizzled family. The authors tested protein constructs containing portions of LIN-18 and found that, whereas the extracellular Wnt binding domain was required for rescue of the lin-18 mutant phenotype, the intracellular kinase domain was not. Mutational analysis and RNAi disruption indicated that the products of three wnt genes, LIN-44, MOM-2, and CWN-2, acted redundantly in this process. Genetic analysis of receptor-ligand and receptor-receptor double mutants led the authors to propose a model in which the two receptors mediated parallel signaling pathways, with LIN-44 preferentially acting through LIN-17 and MOM-2 preferentially acting through LIN-18 to determine cell fate. — EMA

Cell 118, 795 (2004).

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